During the period 01 Oct 08 to 30 Sept 09, significant progress was made on this research project. We found that blockade of brain dopamine D3 receptors by the novel preferential dopamine D3 receptor antagonist S33138 emulates the putative anti-addiction, anti-craving, and anti-relapse efects that we have previously seen with our lead proof-of-concept dopamine D3 receptor antagonist SB277011A. Specifically, we found that S33138 attenuates intravenous cocaine self-administration, attenuates relapse to cocaine-seeking behavior (using the reinstatement animal model) triggered by cocaine, and significantly attenuates drug-enhanced brain reward (as assessed by electrical brain-stimulation reward electrophysiological techniques) produced by cocaine. These effects were seen at low to moderate doses of S33138. At high doses, dopamine D2 antogonist-like effects were observed. These findings add further weight to our previous suggestions that selective dopamine D3 receptor antagonists may be useful in the treatment of drug addiction. With regard to the effects observed with high doses of S33138, we found them to be similar to those that we previously observed with the putative selective D3 antagonist BP897 - and we conclude that the effects of both S33138 and BP897 are likely attributable to a combination of D3 and D2 receptor antagonism. These findings suggest that dopamine D3 receptor antagonists may have anti-addiction, anti-craving, and anti-relapse efficacy in human drug addiction, but that no follow-on D3 antagonist studied to date has the clean anti-addiction profile observed with our lead proof-of-concept compounds SB277011A and NGB2904.